Reriani, Martin

Abstract Mind body therapies appear to reduce morbidity and mortality in patients with cardiovascular diseases, but there is limited understanding of the mechanisms that mediate this effect. Vascular endothelial dysfunction is a central feature of atherogenesis that is adversely impacted by mental stress. We conducted a systematic review and meta-analysis of the effect of mind body therapies on peripheral endothelial function in patients with and without established cardiovascular disease. The search included Medline, Cochrane Library, Scopus and Embase to identify studies up to November 2009. Eligible studies were randomized controlled trials that compared the effects of mind body therapies and placebo on endothelial function. Two reviewers extracted data on study characteristics, methods, and outcomes. Disagreement was resolved by consensus. Three eligible trials enrolled a total of 258 patients. Sixty one (24 percent) were women and 53 percent had established cardiovascular disease. The trials had good methodological quality. Meta-analysis using random-effects model showed a non significant improvement of endothelial function by mind body therapies (standardized mean difference 0.15; 95% CI, -0.36 to 0.67, P=0.56). The analysis was underpowered due to small sample size. Circumstantial evidence indicates that mind body therapies may have a therapeutic benefit on endothelial dysfunction, however, the aggregate data from the three small randomized trials to date do not support this hypothesis. This biologically plausible effect requires additional investigation in adequately powered studies.

Background— Endothelin (ET-1) is one of the most potent vasoconstrictors and plays a seminal role in the pathogenesis of atherosclerosis. The present study was designed to test the hypothesis that long-term treatment with an endothelin-A (ET A ) receptor antagonist improves coronary endothelial function in patients with early coronary atherosclerosis. Methods and Results— Forty-seven patients with multiple cardiovascular risk factors, nonobstructive coronary artery disease, and coronary endothelial dysfunction were randomized in a double-blind manner to either the ET A receptor antagonist atrasentan (10 mg) or placebo for 6 months. Coronary endothelium-dependent vasodilation was examined by infusing acetylcholine (10 −6 to 10 −4 mol/L) in the left anterior descending coronary artery. N G -monomethyl- l -arginine was administered to a subgroup of patients. Endothelium-independent coronary flow reserve was examined by use of intracoronary adenosine and nitroglycerin. Baseline characteristics and incidence of adverse effects were similar between the 2 groups. There was a significant improvement in percent change of coronary blood flow in response to acetylcholine at 6 months from baseline in the atrasentan group compared with the placebo group (39.67%, 95% confidence interval 23.23% to 68.21%, versus −2.22%, 95% confidence interval −27.37% to 15.28%; P <0.001). No significant difference in the percent change of coronary artery diameter or change in coronary flow reserve was demonstrated. Coronary blood flow, coronary artery diameter, and the effect of N G -monomethyl- l -arginine were similar between the groups at baseline and at 6 months. Conclusions— This study demonstrates that 6-month treatment with atrasentan improves coronary microvascular endothelial function and supports the role of the endogenous endothelin system in the regulation of endothelial function in early atherosclerosis in humans. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00271492.